In this proposal, we plan to apply and further develop the FIV/cat system into a model for the study of the effects of drug abuse on lentivirus disease progression. We will examine, in vitro, the effects of morphine on FIV replication and transcriptional rates. We also propose to examine the effects of opiates on the neurological form of the disease in FIV infected cats. It has been suggested that the manner that opiates are delivered to the animal may affect the ultimate outcome of the study. Thus, we plan to examine three morphine scheduling approaches: a single injection, multiple acute injections, and escalating multiple injections, leading to chronic morphine dependence, followed by experimentally enforced withdrawal. The effects of each of these drug schedules on FIV disease progression will be determined by a battery of virological, immunological and functional CNS assays. The information gained from this study will enhance our understanding of opiates as a co-factor in lentivirus pathogenesis. To truly understand disease pathogenesis and the effects co-factors like opiates have on the process, ultimately studies must be conducted in animals. We have developed the FIV/cat system into a legitimate model for studying the effects of lentiviruses on the CNS. Since intravenous drug abuse has become the most common mode of acquiring HIV-1 infections, a greater understanding of the potential effects that drug abuse may have on lentivirus disease progression is urgently needed. Development of the FIV/cat system into a model for the study of the effects of drug abuse on lentivirus disease progression will provide a valuable tool to address this potentially important interaction.